Nicotinic acetylcholine gene cluster CHRNA5-A3-B4 variants influence smoking status in a Bangladeshi population

Nusrat Islam Chaity; Taposhi Nahid Sultana; Md Mehedi Hasan; Ishrat Islam Shrabonee; Noor Ahmed Nahid; Md Saiful Islam; Mohd Nazmul Hasan Apu

doi:10.1007/s43440-021-00243-1

Nicotinic acetylcholine gene cluster CHRNA5-A3-B4 variants influence smoking status in a Bangladeshi population

Pharmacol Rep. 2021 Apr;73(2):574-582. doi: 10.1007/s43440-021-00243-1. Epub 2021 Mar 6.

Authors

Nusrat Islam Chaity¹, Taposhi Nahid Sultana¹, Md Mehedi Hasan¹, Ishrat Islam Shrabonee², Noor Ahmed Nahid¹, Md Saiful Islam¹, Mohd Nazmul Hasan Apu³

Affiliations

¹ Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh.
² Department of Medicine, Mymensingh Medical College Hospital, Mymensingh, 2200, Bangladesh.
³ Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh. nazmul.apu@du.ac.bd.

PMID: 33675519
DOI: 10.1007/s43440-021-00243-1

Abstract

Background: Past studies have established the association of CHRNA5-A3-B4 gene cluster variants with various smoking behaviors in different ethnicities, yet no such study has been reported in Bengali ethnicity to date.

Methods: A case-control study with 129 smokers and 111 non-smokers was conducted and genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method aimed to manifest the association of three SNPs in this gene cluster with smoking status (SS) in a Bangladeshi population.

Results: The non-synonymous CHRNA5 rs1s6969968 and 3'-UTR variant CHRNA3 rs578776 polymorphisms were found to have a strong association with SS. Carriers of polymorphic 'A' allele of rs16969968 showed 1.51-fold more risk of being smokers (adjusted OR = 1.51, 95% CI 0.88-2.57, p = 0.128); whereas, rs578776 polymorphic 'A' allele carriers showed 0.595-fold less risk of being smokers (adjusted OR = 1.51, 95% CI 0.88-2.57, p = 0.006). Comparing smokers and non-smokers, A/A mutant homozygous genotypes of rs578776 and rs16969968 variants pose 0.369-fold (95% CI 0.177-0.77, p = 0.008) and 3.3-fold (95% CI 0.66-16.46, p = 0.14) more risk for positive SS, respectively. No genotypic association for SS was found with intronic variant CHRNB4 rs11072768 (T/G; adjusted OR = 0.827, 95% CI 0.457-1.499, p = 0.532 and G/G; adjusted OR = 0.992, 95% CI 0.455-2.167, p = 0.985). Combination of rs16969968-positive/rs578776-negative polymorphic variants possesses the risk of positive SS in young adults. Furthermore, two new haplotypes (AAT and AAG) were identified in Bangladeshi population and GAG (OR = 0.45, 95% CI 0.25-0.8, p = 0.006) haplotype was found to be a protective factor for SS.

Conclusion: Nicotinic acetylcholine gene cluster CHRNA5-A3-B4 variants rs16969968 and rs578776 are associated with SS in a Bangladeshi population. Large-scale studies are warranted to establish this genotype-phenotype correlation.

Keywords: Bangladeshi population; CHRNA5-A3-B4 gene cluster; Nicotinic acetylcholine receptor; Single-nucleotide polymorphism; Smoking status.

MeSH terms

Adult
Bangladesh
Case-Control Studies
Ethnicity / genetics
Female
Genetic Association Studies
Genetic Variation*
Haplotypes
Humans
Male
Middle Aged
Multigene Family*
Nerve Tissue Proteins / genetics*
Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
Polymorphism, Single Nucleotide
Receptors, Nicotinic / genetics*
Smoking / genetics*
Young Adult

Substances

CHRNA5 protein, human
Nerve Tissue Proteins
Receptors, Nicotinic